Recent studies have elucidated critical molecular mechanisms underlying glioma and neurodevelopmental disorders, particularly focusing on the role of specific genetic mutations and epigenetic factors. Chen et al. demonstrated that histone H3.3 G34R/V mutations, prevalent in gliomas, arise from GSX2/DLX-expressing interneuron progenitors, where these mutations hinder neuronal differentiation. Notably, 50% of G34R/V tumors exhibit activating mutations in PDGFRA, indicating a strong selection pressure during tumor recurrence (ref: Chen doi.org/10.1016/j.cell.2020.11.012/). In pediatric cases, Perwein et al. reported a high frequency of disease progression in spinal cord low-grade gliomas, with KIAA1549-BRAF fusions found in 40% of patients, emphasizing the need for tailored management strategies (ref: Perwein doi.org/10.1093/neuonc/). Wu et al. identified SOX10 as a master regulator of glioblastoma subtypes, linking it to adverse prognosis and therapy-associated transitions, thus highlighting the importance of epigenetic regulation in tumor behavior (ref: Wu doi.org/10.1038/s41467-020-20225-w/). Furthermore, Feng et al. constructed a gene expression-based signature for glioma prognosis, demonstrating its potential clinical utility (ref: Feng doi.org/10.1042/BSR20203051/). These findings collectively underscore the intricate interplay of genetic alterations and epigenetic modifications in glioma pathogenesis and the implications for therapeutic strategies.

Neuroinflammation plays a pivotal role in neurodegenerative diseases, with recent research highlighting the complex interactions between microglia, oligodendrocytes, and neuronal health. Berghoff et al. revealed that microglia facilitate the repair of demyelinated lesions by synthesizing cholesterol, which is essential for new myelin membrane formation, thus indicating a shift from a pro-inflammatory to an anti-inflammatory environment during lesion resolution (ref: Berghoff doi.org/10.1038/s41593-020-00757-6/). In a study by Biechele et al., sex differences in microglial activation were examined, showing that females exhibit higher TSPO-PET binding in response to amyloidosis, suggesting a need for sex-specific considerations in neurodegeneration research (ref: Biechele doi.org/10.1186/s12974-020-02046-2/). Gallego-Delgado et al. further demonstrated that neuroinflammation in the normal-appearing white matter of multiple sclerosis brains leads to structural abnormalities at the nodes of Ranvier, which could contribute to functional deficits (ref: Gallego-Delgado doi.org/10.1371/journal.pbio.3001008/). Additionally, Zhang et al. discussed the role of Ash1l in neurodevelopmental disorders, linking it to shared epigenetic mechanisms in conditions like Tourette syndrome and autism (ref: Zhang doi.org/10.1002/dneu.22795/). Collectively, these studies emphasize the multifaceted nature of neuroinflammation and its implications for neurodegenerative disease progression and potential therapeutic interventions.

Research into amyloid pathology has provided significant insights into the mechanisms underlying Alzheimer's disease (AD) and potential therapeutic targets. Héard et al. explored the transmission of amyloid-β (Aβ) deposits through iatrogenic means, demonstrating that histologically silent Aβ seeds can induce amyloid deposition in transgenic mouse models, highlighting the importance of understanding Aβ propagation (ref: Héard doi.org/10.1186/s40478-020-01081-7/). Van Gerresheim et al. investigated the interaction between insoluble and soluble Aβ, revealing that this interaction could explain the heterogeneity of Aβ plaque loads observed in AD patients, suggesting that soluble Aβ dimers may play a more critical role in cognitive decline than previously thought (ref: van Gerresheim doi.org/10.1111/nan.12685/). De Vidania et al. identified neuroglobin as a protective factor against the initiation of AD pathology, indicating that upregulation of this protein could serve as a potential biomarker or therapeutic target (ref: de Vidania doi.org/10.3389/fnins.2020.562581/). Furthermore, Wu et al. highlighted the potential of tRNA-derived fragments as biomarkers for AD, linking their altered expression to neuropathological mechanisms (ref: Wu doi.org/10.3233/JAD-200917/). These findings collectively underscore the complexity of amyloid pathology in AD and the need for continued exploration of its underlying mechanisms and therapeutic avenues.

The genetic and epigenetic landscape of brain tumors has been increasingly characterized, revealing distinct molecular signatures that inform diagnosis and treatment. Sievers et al. identified clear cell meningiomas as a distinct molecular subtype characterized by specific DNA methylation profiles and mutations in the SMARCE1 gene, emphasizing the importance of molecular classification in treatment strategies (ref: Sievers doi.org/10.1007/s00401-020-02247-2/). Holdhof et al. differentiated atypical teratoid/rhabdoid tumors (ATRTs) with SMARCA4 mutations from those with SMARCB1 mutations, noting that the former are associated with a poorer prognosis and a higher frequency of germline mutations, thus underscoring the need for tailored therapeutic approaches (ref: Holdhof doi.org/10.1007/s00401-020-02250-7/). Zekri et al. reported on an IgG-based bispecific antibody targeting PSMA, which could enhance therapeutic efficacy in PSMA-positive cancers, highlighting the potential for dual-targeting strategies in cancer treatment (ref: Zekri doi.org/10.15252/emmm.201911902/). Additionally, Jiang et al. provided insights into gliosarcoma pathology through advanced imaging techniques, revealing multiple pathological components that complicate diagnosis and treatment (ref: Jiang doi.org/10.7555/JBR.34.20200089/). These studies collectively illustrate the critical role of genetic and epigenetic factors in brain tumor biology and the implications for personalized medicine.

Neurodevelopmental disorders are increasingly linked to disruptions in synaptic function, with recent studies shedding light on the molecular mechanisms involved. Uchigashima et al. demonstrated that specific neuroligin3-neurexin1 signaling is crucial for regulating GABAergic synaptic function in the mouse hippocampus, suggesting that disruptions in this pathway may contribute to neurodevelopmental disorders (ref: Uchigashima doi.org/10.7554/eLife.59545/). Yi et al. explored the role of inactive variants of the p75 neurotrophin receptor in Alzheimer's disease, indicating that these variants may influence the internalization and trafficking of amyloid precursor protein, thereby affecting synaptic integrity (ref: Yi doi.org/10.15252/embj.2020104450/). Lee-Rivera et al. investigated the role of PKC-ζ in retinal pigment epithelium cells, revealing that its pseudosubstrate peptide can induce glutamate release, which may have implications for synaptic signaling in neurodevelopment (ref: Lee-Rivera doi.org/10.1016/j.lfs.2020.118860/). Furthermore, Zhang et al. highlighted the role of Ash1l in neurodevelopmental disorders, linking it to epigenetic factors that may influence synaptic development and function (ref: Zhang doi.org/10.1002/dneu.22795/). These findings collectively emphasize the intricate relationship between synaptic function and neurodevelopmental disorders, paving the way for potential therapeutic interventions.

Recent advancements in therapeutic approaches and biomarker discovery in neuropathology have shown promise for improving patient outcomes. Berghoff et al. highlighted the role of microglia in repairing demyelinated lesions, suggesting that targeting cholesterol synthesis pathways could enhance remyelination in multiple sclerosis (ref: Berghoff doi.org/10.1038/s41593-020-00757-6/). Roux et al. conducted a systematic review on meningioangiomatosis, demonstrating that surgical resection can significantly improve seizure control, thus advocating for timely intervention in this rare condition (ref: Roux doi.org/10.1212/WNL.0000000000011372/). Feng et al. explored the therapeutic potential of mesenchymal-stem-cell-derived extracellular vesicles in mitigating trained immunity in the brain, revealing that IL-10 plays a crucial role in their efficacy (ref: Feng doi.org/10.3389/fbioe.2020.599058/). Additionally, Stančič et al. introduced an innovative blood endothelial cell chamber to study immune responses in drug development, which could enhance the understanding of adverse immune-mediated reactions during immunotherapy (ref: Stančič doi.org/10.1016/j.intimp.2020.107237/). Jiang et al. provided insights into gliosarcoma pathology through advanced imaging techniques, revealing multiple pathological components that complicate diagnosis and treatment (ref: Jiang doi.org/10.7555/JBR.34.20200089/). Collectively, these studies underscore the importance of integrating therapeutic strategies with biomarker discovery to advance the field of neuropathology.

Understanding cellular and molecular responses to injury is crucial for developing effective therapeutic strategies in neurodegenerative diseases. Lohrberg et al. investigated the impact of astrocytic loss on oligodendrocyte precursor cells (OPCs) during demyelination, revealing that the absence of astrocytes hinders OPC maturation and myelination, which is critical for recovery from injuries such as central pontine myelinolysis (ref: Lohrberg doi.org/10.1186/s40478-020-01105-2/). Biechele et al. examined sex differences in microglial activation in mouse models of neurodegeneration, finding that female mice exhibited heightened microglial responses to amyloidosis, suggesting that sex-specific factors may influence neuroinflammatory responses (ref: Biechele doi.org/10.1186/s12974-020-02046-2/). Stančič et al. introduced a novel blood endothelial cell chamber to study immune responses, which could provide insights into the mechanisms underlying immune-mediated reactions in the context of neuroinflammation (ref: Stančič doi.org/10.1016/j.intimp.2020.107237/). Jiang et al. detailed the imaging characteristics of gliosarcoma, highlighting the complexity of its pathology and the need for comprehensive diagnostic approaches (ref: Jiang doi.org/10.7555/JBR.34.20200089/). These findings collectively emphasize the importance of understanding cellular responses to injury and the potential for targeted interventions to enhance recovery and mitigate neurodegeneration.

Neurodevelopmental and genetic disorders are increasingly recognized for their complex genetic underpinnings and the need for precise diagnostic approaches. Tauziède-Espariat et al. evaluated the diagnostic accuracy of a reduced immunohistochemical panel for medulloblastoma molecular subtyping, demonstrating high concordance with DNA-methylation profiling, which could streamline diagnostic processes in pediatric brain tumors (ref: Tauziède-Espariat doi.org/10.1097/PAS.0000000000001640/). Stančič et al. highlighted the importance of understanding immune responses in drug development, particularly in the context of neurodevelopmental disorders, where adverse reactions can complicate treatment (ref: Stančič doi.org/10.1016/j.intimp.2020.107237/). Kelemen et al. reported on eosinophilia in various contexts, emphasizing the need for accurate diagnosis and management strategies in patients with underlying genetic disorders (ref: Kelemen doi.org/10.1093/ajcp/). Rocha et al. described a novel mutation in NEB associated with fetal nemaline myopathy, underscoring the genetic heterogeneity of congenital myopathies and the importance of early genetic diagnosis (ref: Rocha doi.org/10.1016/j.nmd.2020.11.014/). These studies collectively highlight the critical role of genetic and epigenetic factors in neurodevelopmental disorders and the potential for improved diagnostic and therapeutic strategies.